Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease

Abstract

Background and objectives: In autosomal dominant polycystic kidney disease (ADPKD), progressive kidney cyst formation commonly leads to ESRD. Because important manifestations of ADPKD may be evident in childhood, early intervention may have the largest effect on long-term outcome. Statins are known to slow progressive nephropathy in animal models of ADPKD. This randomized double-blind placebo-controlled phase III clinical trial was conducted from 2007 to 2012 to assess the effect of pravastatin on height-corrected total kidney volume (HtTKV) and left ventricular mass index (LVMI) by magnetic resonance imaging (MRI) and urine microalbumin excretion (UAE) in children and young adults with ADPKD.

Designs, setting, participants, & measurements: There were 110 pediatric participants with ADPKD and normal kidney function receiving lisinopril who were randomized to treatment with pravastatin or placebo for a 3-year period with evaluation at 0, 18, and 36 months. The primary outcome variable was a ≥ 20% change in HtTKV, LVMI, or UAE over the study period.

Results: Ninety-one participants completed the 3-year study (83%). Fewer participants receiving pravastatin achieved the primary endpoint compared with participants receiving placebo (69% versus 88%; P=0.03). This was due primarily to a lower proportion reaching the increase in HtTKV (46% versus 68%; P=0.03), with similar findings observed between study groups for LVMI (25% versus 38%; P=0.18) and UAE (47% versus 39%; P=0.50). The percent change in HtTKV adjusted for age, sex, and hypertension status over the 3-year period was significantly decreased with pravastatin (23% ± 3% versus 31% ± 3%; P=0.02).

Conclusions: Pravastatin is an effective agent to slow progression of structural kidney disease in children and young adults with ADPKD. These findings support a role for early intervention with pravastatin in this condition.

Keywords: children; kidney volume; polycystic kidney disease; statins.

Figures

Figure 1.

Courseof study participants. A total of 111 potential participants were screened, including 110 participants who were randomly assigned in a double-blind manner to receive either pravastatin or placebo. A total of 91 participants (83%) completed the 3-year trial. CK, creatine kinase.

Figure 2.

Study endpoints. The primary end point was the percent of participants demonstrating ≥20% increase over the three-year study period in any of the total kidney volume corrected for height (HtTKV), left ventricular mass index (LVMI), or urine microalbumin excretion (UAE) between pravastatin and placebo study groups. Secondary end points included ≥20% increase in these individual variables.

Figure 3.

Percent increase in HtTKV over the course of the study.

Figure 4.

Effect of pravastatin on change in HtTKV.